AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

While any type of glaucoma can be unilateral, primary open-angle glaucoma, primary angle-closure glaucoma, primary infantile glaucoma, juvenile-onset glaucoma, and pigmentary glaucoma are generally bilateral diseases, the severity of which may be asymmetric in the two eyes.

This article reviews glaucoma associated with increased episcleral venous pressure (EVP) and glaucoma associated with iridocorneal endothelial (ICE) syndrome.

Several etiologies of unilateral glaucoma are discussed in detail in other articles, including Glaucoma, Pseudoexfoliation; Glaucoma, Uveitic; Glaucoma, Lens-Particle; Glaucoma, Drug-Induced; Glaucoma, Neovascular; Glaucoma, Intraocular Tumors; Glaucoma, Hyphema; Glaucoma, Angle Recession; and Glaucoma, Malignant.

Pathophysiology

Increased EVP

In the early 1900s, Lauber provided histological evidence that the canal of Schlemm was connected to the episcleral venous network. Aqueous humor drains via the anterior surface of the ciliary body or through the trabecular meshwork, Schlemm canal, collector channels, and, subsequently, aqueous veins. These pathways have been termed unconventional and conventional, respectively.

While the unconventional pathway is independent of pressure, outflow via the conventional route is passive and depends largely on the difference between the intraocular pressure (IOP) and EVP; as EVP increases relative to IOP, or as resistance increases, flow decreases.

The 3 general pathophysiological mechanisms of increased EVP are arteriovenous anomalies, venous obstruction, and idiopathic. Arteriovenous anomalies associated with increased EVP include carotid-cavernous sinus fistula, orbital varix, Sturge-Weber syndrome, orbital-meningeal shunts, carotid-jugular venous shunts, and intraocular vascular shunts. Venous obstruction may be caused by a retrobulbar tumor, thyroid ophthalmopathy, superior vena cava syndrome, congestive heart failure, thrombosis of the cavernous sinus or orbital vein, vasculitis involving the episcleral or orbital vein, and jugular vein obstruction.

ICE syndrome

The pathophysiological mechanism underlying ICE syndrome remains unknown. However, the finding of chronic inflammatory cells in the corneal specimens of patients with ICE syndrome suggests a viral etiology. In a study using polymerase chain reaction techniques, 16 of 25 corneas from patients with ICE syndrome and 4 of 6 patients with herpetic keratitis were positive for herpes simplex virus.

Glaucoma associated with ICE syndrome is believed to be due to trabecular meshwork obstruction caused by peripheral anterior synechiae or, less commonly, an abnormal cellular membrane.

Frequency

United States

The frequency of glaucoma associated with increased EVP or with ICE syndrome is unknown.

Glaucoma has been reported to occur in 30% of patients with Sturge-Weber syndrome, 5% of patients with thyroid ophthalmopathy, 11.6% of patients with scleritis, and 4% of patients with episcleritis.

Mortality/Morbidity

• Glaucoma is the third leading cause of blindness in the United States.
• Because glaucoma may progress insidiously without causing symptoms, progressive glaucomatous damage may occur without the patient even being aware of the diagnosis.
• Prompt and continued control of IOP can prevent ocular damage due to glaucoma.

Sex

• Traumatic carotid-cavernous sinus fistulae occur more commonly in males than in females.
• ICE syndrome occurs more commonly in females than in males.

Age

• Spontaneous carotid-cavernous sinus fistulae typically occur in middle-aged to elderly individuals, while traumatic carotid-cavernous sinus fistulae occur most commonly in young persons.
• It has been reported that 60% of patients with glaucoma associated with Sturge-Weber syndrome acquire glaucoma before age 2 years, and the remaining patients develop glaucoma later in childhood or in early adulthood.
• The onset of ICE syndrome generally occurs in early to middle adulthood.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Elicit history of trauma, thyroid disease, congestive heart failure, vasculitis, malignancy, and other systemic diseases.
• Diplopia may be a presenting complaint of patients with a carotid-cavernous sinus fistula, thyroid ophthalmopathy, or retrobulbar tumor.
• Carotid-cavernous sinus fistulae often present after the following:
• • A severe head injury
  • Any penetrating injury to the orbit injuring the medial or inferomedial wall of the orbit and/or the superior orbital fissure
  • Surgery involving the internal carotid artery
  • Rupture of a preexisting aneurysm of the internal carotid artery

Physical

• Ophthalmic examination
• • Increased EVP may cause pulsating exophthalmos, conjunctival chemosis, engorgement of the episcleral vein, restricted ocular motility, ocular bruit, and ocular ischemia.
  • Dilated episcleral vessels are a prominent feature of Sturge-Weber syndrome; choroidal hemangioma is present in 31-50% of patients with Sturge-Weber syndrome.
  • A common clinical sign of an orbital varix is intermittent exophthalmos (exophthalmos occurring when the head is placed in a dependent position, when the patient sneezes, or when the patient performs a Valsalva maneuver).
  • Orbital tumors may cause proptosis and restricted ocular motility.
  • Thyroid ophthalmopathy may cause proptosis, restricted ocular motility, conjunctival chemosis, epiphora, exposure keratitis, and optic nerve compression.
  • Presenting signs of the superior vena cava syndrome include edema of the lid, face, and conjunctiva; vascular engorgement of the fundus, episclera, and conjunctiva; proptosis; optic nerve edema; and glaucoma.
  • IOP may increase while supine and may decrease while sitting.
  • The most common presenting manifestations of ICE syndrome are iris abnormalities (eg, iris atrophy, corectopia, ectropion uveae, peripheral anterior synechiae, iris nevi), decreased vision, and pain. Other features of the syndrome may include fine-hammered silver appearance of the posterior cornea and corneal edema.

Causes

• Glaucoma associated with EVP is due to increased resistance of aqueous outflow from the Schlemm canal and is associated with arteriovenous anomalies, venous obstruction, and idiopathic anomalies.
• Glaucoma associated with ICE syndrome is believed to be due to trabecular meshwork obstruction caused by peripheral anterior synechiae or, less commonly, an abnormal cellular membrane.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Increased EVP

Orbital fractures
Other traumatic injuries
Underlying malignancy
Thyroid disease
Congestive heart failure
Other systemic diseases (eg, spontaneous carotid-cavernous fistulae have been reported in association with Ehlers-Danlos syndrome and pseudoexfoliation)

ICE syndrome

Corneal edema

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Lab studies are indicated based on the suspected etiology (eg, thyroid function test, vasculitis workup) of unilateral glaucoma.

Imaging Studies

• B-scan echography to evaluate for orbital tumor, foreign body, and extraocular muscle enlargement (in thyroid ophthalmopathy and other conditions with EVP); also indicated if fundus cannot be visualized
• CT scan of orbits to evaluate orbital fracture, foreign body, dilation of superior ophthalmic vein, and enlargement of cavernous sinus (present with carotid-cavernous sinus fistulae)
• Angiography to evaluate for arteriovenous anomalies
• Orbital venography to evaluate for orbital varix
• Color Doppler to evaluate for orbital varix

Other Tests

• In patients with increased EVP, gonioscopic examination may reveal reflux of blood in the Schlemm canal.
• Ocular pulse amplitude, as measured by pneumotonometry, is a useful noninvasive tool to evaluate patients with carotid-cavernous fistulae.
• Malignancy workup for patients with superior vena cava syndrome, orbital tumors
• Cardiac workup for patients with congestive heart failure

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• Increased EVP
• • Although topical glaucoma medications and oral carbonic anhydrase inhibitors may be used initially to control IOP, the underlying etiology must be resolved to achieve long-term IOP control.
  • Medications that decrease aqueous production are more effective than drugs that increase aqueous outflow.
• ICE syndrome
• • Medications that reduce aqueous production can often control the early stages of glaucoma.
  • Epinephrine may be effective in some cases.
  • The benefit of topical prostaglandins remains to be demonstrated.
  • Miotics are generally ineffective due to mechanical obstruction of the trabecular meshwork.

Surgical Care

• Increased EVP
• • Laser trabeculoplasty is generally ineffective unless there are secondary changes in the outflow channels.
  • Glaucoma filtering surgery may be necessary in cases refractory to medical therapy to completely bypass the resistance due to increased EVP; ciliochoroidal effusions or suprachoroidal hemorrhage may complicate filtering surgery.
  • The optimal treatment of a direct carotid-cavernous sinus fistula is closure of the abnormal arteriovenous communication with preservation of internal carotid artery patency. Techniques to achieve this result include surgical repair of the damaged portion of the intracavernous internal carotid artery, electrothrombosis, embolization, or balloon occlusion of the fistula.
  • Dural carotid-cavernous sinus fistulae may close spontaneously, but, for those lesions causing progressive or unacceptable symptoms and signs, standard embolization or endovascular balloon occlusion is generally performed. If these techniques are unsuccessful, direct surgery on the cavernous sinus may be considered. In cases where anatomy makes a standard intravascular approach impossible, the superior ophthalmic vein can be cannulated and a balloon or coil can be threaded into the area of a direct communication.
• ICE syndrome
• • Laser trabeculoplasty is usually ineffective.
  • Patients with ICE syndrome generally do well with glaucoma filtering surgery, although late failure may develop due to endothelialization of the fistula, which, in some cases, may be reopened with the Nd:YAG laser.

Consultations

• Increased EVP
• • Consultation is indicated depending on the coexisting conditions.
  • Oculoplastic consultation for management of orbital tumors
  • Vitreoretinal consultation for management of choroidal hemangiomas
  • Patients with thyroid ophthalmopathy may benefit from neuro-ophthalmic and/or oculoplastic consultation for management of optic neuropathy.
  • Corneal consultation for management of exposure keratitis
• ICE syndrome - Cornea consultation for management of corneal edema

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medications used to decrease aqueous production include beta-blockers (topical), carbonic anhydrase inhibitors (topical and/or oral), and alpha 2-agonists.

Drug Category: Beta-adrenergic blockers

Decrease IOP by reducing aqueous production. Reduce elevated and normal IOP, with or without glaucoma.

Drug Category: Alpha 2-adrenergic agonists

Act to decrease aqueous humor formation.

Drug Category: Carbonic anhydrase inhibitors

Enzyme found in many tissues of the body, including the eye. Catalyzes a reversible reaction where carbon dioxide becomes hydrated and carbonic acid dehydrated. By slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport, it may inhibit CA in the ciliary processes of the eye. This effect decreases aqueous humor secretion, reducing IOP.

Drug Category: Prostaglandin derivatives

These agents may decrease intraocular pressure by increasing the outflow of aqueous humor.

They are administered once per day (except for unoprostone, which is administered twice daily). Potential adverse effects of these medications are similar to latanoprost (eg, eyelash growth, increased iris pigmentation). These agents are considered by some glaucoma specialists as first-line agents for glaucoma, mainly because of the lack of systemic adverse effects.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Outpatient Care

• Close monitoring of IOP and vigilance for evidence of glaucomatous injury (as manifested by examination of the patient's optic discs and by visual field testing) are warranted.

Complications

• If the patient does not comply with the use of medications, further deterioration of the visual field may occur.

Prognosis

• The prognosis for glaucoma is favorable if IOP can be maintained over the lifetime of the patient.

Patient Education

• For excellent patient education resources, visit eMedicine's Glaucoma Center. Also, see eMedicine's patient education articles Glaucoma FAQs and Understanding Glaucoma Medications.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Prompt diagnosis and complete treatment of glaucoma are important to arrest further deterioration of the visual field.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Albert DM, Jakobiec FA, Azar DT. Glaucoma associated with increased episcleral venous pressure. In: Principles and Practice of Ophthalmology. 2nd ed. WB Saunders Co;2000: 2781-2792.
• Alvarado JA, Underwood JL, Green WR, et al. Detection of herpes simplex viral DNA in the iridocorneal endothelial syndrome. Arch Ophthalmol. Dec 1994;112(12):1601-9. [Medline].
• Cibis GW, Tripathi RC, Tripathi BJ. Glaucoma in Sturge-Weber syndrome. Ophthalmology. Sep 1984;91(9):1061-71. [Medline].
• Font RL, Ferry AP. The phakomatoses. Int Ophthalmol Clin. 1972;12(1):1-50. [Medline].
• Gandolfi SA, Cimino L, Sangermani C, et al. Improvement of spatial contrast sensitivity threshold after surgical reduction of intraocular pressure in unilateral high-tension glaucoma. Invest Ophthalmol Vis Sci. Jan 2005;46(1):197-201. [Medline].
• Jain SS, Rao P, Kothari K, et al. Posterior scleritis presenting as unilateral secondary angle-closure glaucoma. Indian J Ophthalmol. Sep 2004;52(3):241-4. [Medline].
• Kirsch M, Henkes H, Liebig T, et al. Endovascular management of dural carotid-cavernous sinus fistulas in 141 patients. Neuroradiology. Jul 2006;48(7):486-90. [Medline].
• Manor RS, Kurz O, Lewitus Z. Intraocular pressure in endocrinological patients with exophthalmos. Ophthalmologica. 1974;168(4):241-52. [Medline].
• Uram M, Zubillaga C. The cutaneous manifestations of Sturge-Weber syndrome. J Clin Neuroophthalmol. Dec 1982;2(4):245-8. [Medline].
• Watson PG, Hayreh SS. Scleritis and episcleritis. Br J Ophthalmol. Mar 1976;60(3):163-91. [Medline].
• Weiss DI. Dual origin of glaucoma in encephalotrigeminal haemangiomatosis. Trans Ophthalmol Soc U K. 1973;93(0):477-93. [Medline].

Article Last Updated: Mar 8, 2007